Targeting intrinsically disordered proteins at the edge of chaos

被引:102
作者
Ruan, Hao [1 ]
Sun, Qi [1 ]
Zhang, Weilin [1 ]
Liu, Ying [1 ,2 ]
Lai, Luhua [1 ,2 ,3 ]
机构
[1] Peking Univ, BNLMS, Coll Chem & Mol Engn, State Key Lab Struct Chem Unstable & Stable Speci, Beijing 100871, Peoples R China
[2] Peking Univ, Ctr Quantitat Biol, Beijing 100871, Peoples R China
[3] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
基金
中国国家自然科学基金;
关键词
SMALL-MOLECULE; DRUG DISCOVERY; UNSTRUCTURED PROTEINS; BINDING; CANCER; INHIBITOR; ONCOPROTEIN; ACTIVATION; PREDICTION; COMPLEXES;
D O I
10.1016/j.drudis.2018.09.017
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Intrinsically disordered proteins or intrinsically disordered regions (IDPs or IDRs) are those that do not fold into defined tertiary structures under physiological conditions. Given their prevalence in various diseases, IDPs are attractive therapeutic targets. However, because of the dynamic nature of the IDP structure, conventional structure-based drug design methods cannot be directly applied. Thanks to recent progress in understanding the mechanisms underlying IDP and ligand interactions, computational strategies for IDP-targeted rational drug discovery are emerging. Here, we summarize recent developments in computational IDP drug design strategies and their successful applications, analyze the typical properties of reported IDP-binding compounds (iIDPs), and discuss the major challenges ahead as well as possible solutions.
引用
收藏
页码:217 / 227
页数:11
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